Predicting relapse and recovery

Addiction is another challenging medical problem that is slowly revealing its secrets to brain imaging.

Through the use of PET and, more recently, fMRI, scientists are beginning to define—anatomically and biochemically—what drugs of abuse do to the brain.

“We’ve known for probably 30 years or more that using drugs like alcohol for long periods of time causes injury to the brain,” says Peter Martin, M.D., professor of Psychiatry and Pharmacology and director of the Division of Addiction Medicine in the Department of Psychiatry at Vanderbilt.

In computerized tomography (CT) scans, for example, “the brains of alcoholics seem to have shrunk compared to normal,” he says. Yet images of the brain’s structure don’t correlate well with impairments detected in neuropsychological tests. So, in the early 1990s, “we started looking at what was happening chemically in those regions of the brain that shrink.”

Martin and his colleagues used a magnetic resonance technique called MR spectroscopy to measure several brain chemicals including N-acetylaspartate (NAA), which is found primarily inside neurons (nerve cells). The researchers detected lower levels of NAA in the cerebellum in alcoholics, compared to normal controls, suggesting the presence of damaged or dying neurons.

The cerebellum, located at the base of the skull, controls muscle tone, balance and fine movement coordination. It also transmits signals to the prefrontal cortex behind the eyes, which plays key roles in working memory and judgment, as well as emotion, arousal and attention.

Levels of NAA were lowest—indicating the greatest amount of neuron damage—in the cerebella of patients who had started drinking heavily at an earlier age and who had a family history of alcoholism. These patients also relapsed earlier after a period of abstinence than did alcoholics with higher NAA levels, the researchers reported in 2002.

“It’s almost as if their brains were more sensitive to developing brain injury,” concludes Martin. “In the future, we may be able to do spectroscopy and predict which patients will do well and which ones will not.”

Imaging technologies such as fMRI not only can record damage done by drugs; they are shedding light on the processes in the brain—including reward, motivation, memory and craving—that can lead to and maintain addictive behavior.

Functional MRI measures the magnetic properties of hemoglobin, the iron-bearing oxygen transporter in red blood cells. Activation of part of the brain increases the demand for oxygen, and thus the intensity of the intensity of the magnetic signal.

Ronald L. Cowan, M.D., Ph.D., assistant professor of Radiology and Radiological Sciences at Vanderbilt, is using fMRI to study how brain activation changes over time in response to amphetamine, a powerful stimulant.